Herpes simplex virus 1 (HSV-1) causes life-long infection and periodic disease in the majority of the world's human population (see, e.g., Corey, Herpes Simplex Viruses, in Braunwald et al., Eds., Harrison's Principles of Internal Medicine. 15th ed. New York: McGraw Hill, 2001, Chap. 182, pp. 1100-1106; and Whitley et al., N. Engl. J. Med., 324: 450-4 (1991)). Herpes group viruses (including HSV, VZV, and CMV), usually cause only limited disease in adults and older children.
In humans, HSV-1 is usually acquired in childhood, and often presents as a self-limiting pharyngitis. Reactivation of HSV-1 infection is associated with peri-oral lesions, sometimes termed “cold sores” or “fever blisters.” Neonates (most often at less than one week of age) with HSV (either HSV-1 or HSV-2) infections, however, may present with a “sepsis-like” syndrome that, although rare, can be devastating, and is often characterized by blood pressure instability, shock, fever, jaundice, hepatosplenomegaly, and the development of disseminated intravascular coagulation, symptoms commonly seen in serious TORCH infections (Toxoplasmosis, Other infections, Rubella, Cytomegalovirus, and Herpes) (Id.), as well as lethal encephalitis (Whitely, 2001, in Fields' Virology, Knipe, ed., Chapter 73, Lippincott, Williams, & Wilkins, Philadelphia, Pa.; Whitley et al., N. Engl. J. Med. 324: 450-454 (1991)). Herpes simplex virus type 2 (HSV-2) is a major cause of neonatal encephalitis. The primary route of infection is via the maternal birth canal, although, infrequently, hematogenous transplacental in utero infection can occur. The CNS is involved in approximately 30% of infected infants. Infection can result in seizures, microcephaly, microphthalmia, ventriculomegaly, multicystic encephalomalacia and death. Pathological examination demonstrates acute and chronic parenchymal and leptomeningeal inflammation. In contrast to the temporal/frontal predilection seen in adults, HSV neonatal infection is diffuse and may therefore result in widespread brain destruction.
Herpes simplex 1 (HSV-1) is also the most common diagnosed cause of sporadic (non-epidemic) encephalitis in humans. Without early treatment, HSV-1 encephalitis is a devastating disease that is typically fatal. Among survivors, serious residual defects are commonly seen. While HSV causes a variety of illnesses in immunocompromised hosts, including disseminated infection, pneumonia, and hepatitis, encephalitis is also commonly seen in patients with normal immune responses.